The objective of this grant is to analyze the neural pathways involved in central regulation of the cardiovascular system. Using neuroanatomical transport techniques, we wish to study the efferent connections of specific subnuclei of the nucleus tractus solitarius. The efferent connections of the rostral, intermediate, and caudal regions of the ventral medulla oblongata will be studied with both anterograde and retrograde transport techniques. In some experiments, these will be combined with immunohistochemical methods. The role of substance P in central control of blood pressure will be examined. The descending ventral medulla substance P pathway which appears to regulate the sympathetic outflow will be examined. The objective will be to determine if substance P is synthesized and transported from the ventral medulla to the intermediolateral cell column. The presence of substance P receptors on sympathetic preganglionic neuron will be studied in normal and spontaneously hypertensive rats. Inhibitors of substance P will be used to determine potential differences in blood pressure regulation in hypertensive and normotensive rats. Finally, the regional vascular flow patterns and cardiac output will be examined after chemical excitation of the ventral medulla in normal, sympathectomized, and midbrain transected rats.